title: The anti-inflammatory mechanism of prostaglandin e2 receptor 4 activation in rat experimental autoimmune myocarditis.
abstract: Prostaglandins (PG) and their specific receptors for E type PG (EP) play an important role in inflammatory diseases. Although myocarditis results in inflammation of the heart, roles of PG and EP in its pathophysiology is still controversial. To clarify the role of PG and EP on the progression of myocarditis, we used an experimental autoimmune myocarditis model. A selective EP4 (EP4RAG) agonist was administered into both early (Day 0 to 21) and late (Day 14 to 21) -treated groups and the animals were killed on Day 21. We found that improved cardiac function was detected in the EP4RAG-treated groups in comparison to the untreated group. The infiltration area ratio in the early-treated (16.6% ± 4.6%) group was lower than those in the untreated group (32.1% ± 3.5%) (P < 0.05). The fibrosis area ratios in the early-treated (19.2% ± 6.3%) and the late-treated groups (24.4% ± 5.1%) were lower than those in the untreated group (37.4% ± 2.6%), respectively (P < 0.05). Moreover, we found that EP4RAG decreased T-cell proliferation and monocyte chemoattractant protein-1 production in vitro. We concluded that a selective EP4 agonist inactivates T-cells, which turns out to moderate the progression of experimental autoimmune myocarditis. Therefore, EP4 can be an effective target for myocarditis treatment.
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Pham Bao
authors.initials: PB
authors.lastname: Ngoc
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Suzuki
authors.forename: Masahito
authors.initials: M
authors.lastname: Ogawa
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hishikari
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takayama
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Hirata
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Isobe
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D009202:Cardiomyopathies / Q000188:drug therapy; D049109:Cell Proliferation / Q000187:drug effects; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D009205:Myocarditis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D009218:Myosins / Q000009:adverse effects; D051381:Rats; D011917:Rats, Inbred Lew; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000819:agonists* / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: C561620:17,18,19,20-tetranor-16-(3-biphenyl)-2,3,13,14-tetradehydroprostaglandin E1; D000893:Anti-Inflammatory Agents; D058309:Receptors, Prostaglandin E, EP4 Subtype; D009218:Myosins; D000527:Alprostadil; D015232:Dinoprostone